Genetic testing for BRCA1 and BRCA2 (BRCA1/2) mutations is part of routine clinical care for women with a family history of breast or ovarian cancer. However, a mutation in these genes is not identified in most women who pursue testing. Such "uninformative" results do not rule out the possibility of an inherited susceptibility to these cancers. The absolute risks for breast and ovarian cancer are heterogeneous and must be estimated based upon an analysis of the family pedigree. Given this complexity, there are currently no standard counseling approaches, risk estimation models, or risk management guidelines for BRCA1/2 uninformatives. Moreover, the resulting uncertainty has been associated with distress. Even though women with uninformative results may not be at the highest risk of developing a primary or contralateral breast cancer or ovarian cancer, a substantial proportion consider risk reducing surgery (RRS), and decisional conflict regarding management decisions is comparable to those of BRCA1/2 mutation carriers. High-risk uninformatives who do not pursue RRS may be advised to follow an enhanced surveillance regimen similar to BRCA1/2 carriers. To date it is not known whether these women adhere to these guidelines. The goal of this randomized controlled trial is to develop and evaluate an adjunct web-based intervention (AWI) to be administered after post-test genetic counseling (usual care, UC). We will evaluate the relative impact of UC versus UC + AWI on psychosocial, quality of life, and management outcomes, thus addressing innovative questions regarding the 'value-added' of an adjunct intervention over and above UC for BRCA1/2 uninformatives. Guided by the Ottawa Framework and Baum's model of adaptation to genetic testing, we will assess the mechanisms by which AWI impacts patient outcomes and identify women most and least likely to benefit from the AWI intervention. This intervention has the potential to benefit uninformatives - the largest subgroup of BRCA1/2 testing participants. If effective, this intervention could be disseminated to the thousands of women who receive uninformative test results annually. The results of this study will be broadly transportable to other high-risk populations who also receive uninformative genetic test results. As we move toward "personalized" medicine, uninformative test results will become increasingly common, making interventions such as this increasingly relevant. PUBLIC HEALTH RELEVANCE: This study will design and assess an adjunct Web-based intervention for women who receive uninformative BRCA1/2 gene testing results, and in whom increased risks for breast and ovarian cancer are heterogeneous. By facilitating informed decision making, it is hoped that these women will implement breast and ovarian cancer risk management decisions appropriate to their risk level, leading to positive effects on well being and quality of life, and ultimately, to reduced morbidity and mortality from these cancers. [unreadable] [unreadable] [unreadable]